Lecture 12 - Renal Regulation of Acid-Base Balance Flashcards

1
Q

In what 2 forms do the kidneys excrete H+ from the ECF? Which one predominates? Provide daily amounts.

A
  1. Titratable acid: 10 to 30 mEq/day

2. ***Ammonium (NH4+): 30 to 50 mEq/day

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2
Q

Equation for net acid excretion? Unit?

A

NAE (mEq/day) = (UTA.V + UNH4+.V) - UHCO3-.V

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3
Q

Normal net acid excretion?

A

40-80 mmol/day

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4
Q

Describe the pH of tubular fluid.

A

Tubular fluid at bowman’s space has the same pH as plasma (7.4) and will be acidified to be excreted as acid

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5
Q

What is titratable acid?

A

To determine that amount in urine we just add base until the pH has reached 7.4 (titration), which is why we called it that = urinary buffers that can accept H+

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6
Q

Why doesn’t urine titration capture urine NH4+?

A

Because the pKa of NH4+ is >9

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7
Q

9 factors regulating renal acid excretion?

A
  1. GFR
  2. Tubular HCO3- reabsorption
  3. H+ secretion
  4. Ammoniagenesis
  5. PCO2
  6. ECF volume
  7. K+ balance
  8. Aldosterone
  9. Ang II
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8
Q

How does GFR regulate renal acid excretion?

A

As GFR falls, the kidney’s ability to excrete an acid load will decrease

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9
Q

Describe tubular HCO3- reabsorption/secretion to regulate renal acid excretion.

A
  1. PCT and THICK ASCENDING LIMB: Na+/H+ exchanger: H+ is secreted and reacts with HCO3- to form H2O and CO2 by lumenal carbonic anhydrase, which diffuse into the proximal tubule cells. HCO3- in then reformed by carbonic anhydrase inside the cell and exits via the basolateral membrane via facilitated diffusion => NET EFFECT: 1 Na+ reabsorbed = 1 H+ pumped out = 1 HCO3- reabsorbed
  2. Collecting duct:

2a. ALPHA-intercalated cell:
- H+-ATPase: H+ is secreted and reacts with HCO3- to form H2O and CO2 by lumenal carbonic anhydrase, which diffuse into the proximal tubule cells. HCO3- in then reformed by carbonic anhydrase inside the cell and exits via the basolateral membrane via Cl-/HCO3- exchanger => NET EFFECT: H+ pumped out = 1 HCO3- reabsorbed

2b. BETA-intercalated cell:
- HCO3-/Cl- lumenal exchanger with H+-ATPase on the basolateral side: H2O and CO2 converted to HCO3- and H+ by carbonic anhydrase inside the cell and then HCO3- is secreted into lumen and H+ is reabsorbed by the blood

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10
Q

Where is HCO3- reabsorbed in the nephron? Provide %.

A
  1. Proximal tubule: 85%
  2. Thick ascending limb of loop of Henle: 10%
  3. Collecting duct: 5%
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11
Q

Excretion fraction of HCO3-?

A

0% (unless we are on a vegan diet or ingest excess base)

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12
Q

Permeability of HCO3- in proximal tubule and thick ascending limb of the loop of Henle?

A

HCO3- is impermeable intra and paracellularly

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13
Q

What hormone stimulates the reabsorption of HCO3-? Explain how.

A

Angiotensin II:

  1. Stimulates Na+/H+ exchanger in the proximal tubule and thick ascending limb of the loop of Henle
  2. Stimulate H+ secretion via H+ ATP-ase pump insertion on lumenal membrane of intercalated cells of collected duct causing more Na+ reabsorption on the lumenal surface => causing the Na+/K+-ATPase to pump more Na+ out on basolateral suface => further Na+ reabsorption
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14
Q

pH of tubular fluid in early distal tubule? Implication

A

6.8

Ideal buffer at this point is HPO42-/H2PO4- because its pKa = 6.8

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15
Q

Concentration of FREE H+ in maximally acidified urine? What does this mean for urine acid?

A

[H+] = 10^(-4.4) = 0.04 mmol/L

Means that only 0.06 mmol of free H+ excreted in a day => most acid in the urine is NOT free but bound to urinary buffers

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16
Q

What are urinary buffers? What is this referred to in urine?

A
  1. HPO42-
  2. SO42-

=> titratable acids

17
Q

Are the set amounts of alpha and beta intercalated cells in the collecting duct?

A

NOPE - ability of intercalated cells to adjust:

Acidosis => H+-ATPase vesicles migrate to lumenal membrane and HCO3-/Cl vesicles migrate to the basolateral membrane => alpha-intercalated cell

Alkalosis => H+-ATPase vesicles migrate to basolateral membrane and HCO3-/Cl vesicles migrate to the lumenal membrane => beta-intercalated cell

18
Q

Where does H+ being secreted by the proximal tubule/TAL/CD to create TAs come from? Purpose?

A

Comes from CO2 + H2O reacting to form H+ + HCO3- => NEW HCO3- reabsorbed by the peritubular plasma to restore the lost plasma base used to buffer the acid load

19
Q

Purpose of ammoniagenesis?

A

Amount of urinary buffers in tubular fluid is limited (Pi excretion is regulated based on Pi needs, not AB status), so we need another way to accept H+ and excrete it

20
Q

Describe renal ammoniagenesis. Result?

A
  1. Glutaminase: glutamine => glutamate + NH4+
  2. Glutamate dehydrogenase: glutamate => alpha-ketoglutarate + NH4+

RESULT: NH4+ excreted and HCO3- generated

21
Q

How does excreting NH4+ spare HCO3-? Which reason do we use to account for it?

A

TWO REASONS

REASON 1:
Production of urea in the liver: NH4+ + CO2 => urea + 2 H+ => 2H+ need to be buffered by 2 HCO3-
BUT, if you excrete NH4+ directly, without converting it to urea, then you spare those 2 HCO3- => aka you kinda generate them

REASON 2:****
As NH4+ goes through the nephron, in the thick ascending limb, NH4+ takes the place of K+ in the Na+/K+/2Cl- carrier => in the cell it splits into ammonia (NH3) and H+ => H+ used to reabsorb HCO3- through the H+/Na+ exchanger and NH3+ diffuses in outer medulla and into the collecting duct => H+ secreted by intercalated cells reacts with NH3 to produce NH4+ and a NEW HCO3- which is reabsorbed

22
Q

Purpose of urea?

A

Protein excretion

23
Q

What segment of nephron performs ammoniagenesis? How is it secreted into the lumen?

A

Proximal tubule

NH4+ takes the place of H+ in the Na+/H+ lumenal exchanger

24
Q

Ammonia?

A

NH3

25
Q

Ammonium?

A

NH4+

26
Q

Can NH4+ diffuse into tubular cells?

A

NOPE

27
Q

Can ammonia diffuse into tubular cells?

A

YUP

28
Q

How does PCO2 regulate renal acid secretion?

A

Increase in PCO2 => increase in H+ secretion and HCO3- rebsorption (NOT NEW) and production (NEW)

29
Q

How does ECF volume regulate renal acid secretion?

A

Body is faced with making a choice and favors ECF volume balance over AB status:

  1. Expanded volume => decrease Na+ reabsorption => decrease in H+ secretion and decrease in HCO3- reabsorption
  2. Volume contraction => increase Na+ reabsorption => increase in H+ secretion and increase in HCO3- reabsorption
30
Q

How does K+ balance regulate renal acid secretion?

A

Alpha-intercalated cell of the collecting duct allows K+ reabsorption via K+ primary active transport: simple K+ pump => so if K+ reabsorption increases, H+ secretion increases and vice versa

31
Q

How does aldosterone regulate renal acid secretion?

A

ACTS ON COLLECTING DUCT intercalated cells:

  1. Increases K+ secretion => potential K+ depletion => increased H+ secretion by intercalated cells
  2. Direct increase in H+ secretion by stimulating H+ ATP-ase pump insertion on lumenal membrane
32
Q

Does the amount of titratable acids in the urine increase during diabetic acidosis? Explain.

A

Well you would think not, since we said that the amount of urinary buffers in tubular fluid is limited (Pi excretion is regulated based on Pi needs, not AB status)

BUT the ketoacids generated by this diseased state can actually also act as urinary buffers and accept H+

33
Q

How is the acid-base renal regulation affected by chronic renal disease?

A

Loss of renal mass => loss ability of kidney to produce ammonium + low GFR so low titratable acids (but more than ammonium) => metabolic acidosis => need for diet changes to adapt to this challenge

34
Q

How do the amounts of TA and ammonium in urine increase if acid load is increased over days? How is the urinary pH affected?

A

Both increase together in first day, until TA maxes out and then only ammonium concentration increases

pH: drops at first, and then slowly increases back to normal due to increased ammonium production

35
Q

How does plasma bicarbonate change if acid load is increased over days? What to note?

A

First sudden decrease due to buffering, and then slow increase as NH4+ and H+ secretion occurs in the kidney to increase HCO3- production

This cannot bring the levels back to normal if the excess acid load is still coming in BECAUSE THE LAG PHASE OF NH4+ AND H+ SECRETION CAUSED A NET LOSS OF HCO3-

36
Q

What does a negative acid excretion mean?

A

Base is being excreted

37
Q

Is it harder to excrete base or acid for the kidney?

A

Acid because need to generate NH4+ and TA, vs simply not reabsorbing HCO3-

38
Q

Which is larger: HCO3- reabsorption or HCO3- generation?

A

Reabsorption is MUCH larger than generation